Pharmaceutical residues in aquatic ecosystems pose significant environmental and public health challenges. Identifying the presence and levels of these pharmaceuticals is crucial. This study developed an analytical method to detect pharmaceuticals used for Alzheimer’s (AD) and Parkinson’s (PD) disease, including psychiatric drugs and the stimulant caffeine, targeting 30 compounds. Optimized mass spectrometric and liquid chromatographic parameters enabled robust detection and quantification. The methodology was applied to 25 surface and wastewater samples. Twenty-one compounds were detected including eight psychiatric drugs, five metabolites (citalopram N-oxide, citalopram propionic acid, desmethylcitalopram, O-desmethylvenlafaxine, and 10,11-epoxycarbamazepine), and seven AD/PD pharmaceuticals along with caffeine. Nine compounds (apomorphine, benserazide, donepezil, didemethylcitalopram, carbidopa, norfluoxetine, galantamine, pramipexole, and safinamide) were not detected. Fluoxetine was found in all samples, and caffeine had the highest concentration at 76,991 ng/L, reflecting its high consumption. Concentrations ranged from 29.8 to 656 ng/L for caffeine, <MDL to 381 ng/L for psychiatric drugs, and <MDL to 37.1 ng/L for AD and PD pharmaceuticals in surface water. In wastewater, concentrations ranged from 140 to 76,991 ng/L for caffeine, <MDL to 5227 ng/L for psychiatric drugs, and <MDL to 206 ng/L for AD and PD pharmaceuticals. These findings highlight the critical need for comprehensive environmental monitoring.